Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination.
Cell
; 166(1): 102-14, 2016 Jun 30.
Article
in En
| MEDLINE
| ID: mdl-27293192
ABSTRACT
Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Transposable Elements
/
Evolution, Molecular
/
V(D)J Recombination
/
Lancelets
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2016
Type:
Article